Advances in Biomedical Research: Novel Therapeutic and Diagnostic Approaches

Vascularity and the Fibrovascular Interface in Interstitial Lung Diseases

Within interstitial lung diseases (ILDs), a growing body of evidence suggests that vascular remodeling is not merely a bystander effect; rather, it plays an active role in the progression and severity of fibrotic lung damage. Studies have demonstrated that in idiopathic pulmonary fibrosis (IPF), for example, specific morphological changes such as blind‑ending vessels, increased vessel diameters, and an aberrant capillary density are intricately connected with fibroblast activation and extracellular matrix (ECM) deposition. Advanced imaging techniques—such as high‑resolution computed tomography and scanning electron microscopy of corrosion casts—allow researchers to characterize these microvascular changes in detail. Furthermore, molecular studies have identified the involvement of key growth factors like vascular endothelial growth factor (VEGF), transforming growth factor‑β (TGF‑β), and connective tissue growth factor (CTGF) in regulating the balance between angiogenesis and fibrosis. This improved understanding of the fibrovascular interface may lead to the identification of novel targets for therapeutic intervention aimed at halting or reversing fibrotic progression in ILDs.

Recombinant Yeast-Based Oral Vaccines Against F4+ ETEC Infection

The use of recombinant microorganisms as carriers for vaccine antigens has emerged as a promising strategy to combat infectious diseases. One innovative approach involves genetically engineering Saccharomyces cerevisiae (strain EBY100) to express the FaeG subunit—a critical adhesin determinant of F4+ enterotoxigenic Escherichia coli (ETEC). In this system, the FaeG gene is inserted into the shuttle vector pYD1 and displayed on the yeast cell surface by fusion with the Aga2 protein. Experimental validation using Western blotting, immunofluorescence, and flow cytometry confirms the efficient surface expression of the recombinant protein.

Animal studies involving oral immunization of mice have demonstrated that administration of the recombinant yeast vaccine does not compromise yeast growth or induce adverse effects. Moreover, immunized animals show significantly enhanced systemic IgG and mucosal secretory IgA titers compared with control groups. In addition, histological analyses of the small intestine indicate that vaccinated mice exhibit improved villus architecture and an upregulation of tight junction proteins—factors that directly correlate with reinforced gut mucosal immunity. Challenge experiments further reveal that mice immunized with the EBY100/pYD1‑FaeG vaccine have reduced bacterial loads in key tissues and improved survival rates following exposure to pathogenic F4+ ETEC strains. These findings support the potential of recombinant yeast oral vaccines as a cost‑effective and scalable strategy for preventing enteric infections that lead to post‑weaning diarrhea in livestock.

Endogenous Salusins as Biomarkers in Irritable Bowel Syndrome

Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, is characterized by chronic abdominal pain and altered bowel habits. Although traditionally regarded as a disorder without overt inflammation, emerging evidence points to the presence of low‑grade inflammation in affected individuals. Salusins, which are bioactive peptides derived from the precursor prosalusin, have garnered attention for their roles in modulating inflammatory responses, vascular tone, and oxidative stress.

Recent research has focused on measuring serum salusin levels in patients with different IBS subtypes—particularly those with diarrhea‑predominant (D‑IBS) and constipation‑predominant (C‑IBS) forms. Data indicate that salusin‑α levels may be altered in D‑IBS patients, potentially reflecting a dysregulated inflammatory state and disturbed gut–brain interactions. Given that salusins are detectable in bodily fluids and have been linked to various inflammatory and vascular conditions, they represent promising candidate biomarkers for IBS. In clinical settings, reliable biomarkers such as salusin‑α could facilitate early diagnosis, inform prognosis, and potentially guide personalized treatment strategies for patients exhibiting subtle mucosal inflammation.

3′‑Deoxytubercidin: A Promising Therapeutic Candidate for Surra and Dourine

Surra and Dourine are significant trypanosomiasis diseases affecting a wide range of mammals, including economically important livestock such as camels, equids, cattle, and buffaloes. Caused by Trypanosoma brucei evansi and Trypanosoma brucei equiperdum respectively, these diseases pose severe challenges due to their broad host range and limitations associated with current therapeutic options. Existing drugs are hampered by toxic side effects, limited efficacy in neurological stages, and emerging drug resistance.

Recent preclinical studies evaluating the nucleoside analog 3′‑deoxytubercidin have shown outstanding efficacy in mouse models of both Surra and Dourine. When administered intraperitoneally over a five‑day course, 3′‑deoxytubercidin effectively clears parasitemia, leading to full recovery of infected mice without detectable toxicity. In addition to its therapeutic effectiveness, 3′‑deoxytubercidin demonstrates promising characteristics such as the ability to potentially cross the blood–brain barrier, thereby addressing the challenge of treating central nervous system involvement. Complementary ecotoxicological assessments using aquatic organisms such as Daphnia magna and the green alga Desmodesmus subspicatus indicate that the compound exhibits a much lower environmental toxicity compared with mainstream agents like ivermectin. Collectively, these results highlight 3′‑deoxytubercidin’s potential as a safe and potent treatment for Surra and Dourine, with the prospect of broad-spectrum activity against diverse trypanosome species.

Immune Checkpoint Inhibitors in Cancer Patients With Autoimmune Diseases

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by reinvigorating the host immune system to combat tumors. However, their application is associated with immune‑related adverse events (irAEs), particularly in patients with preexisting autoimmune conditions. Given that these patients are often excluded from traditional clinical trials, the safety and efficacy of ICIs in such populations require careful investigation.

A comprehensive meta‑analysis of 52 studies has provided important insights into this topic. Overall, the incidence of any‑grade irAEs in cancer patients with autoimmune diseases was estimated at approximately 61%, while severe (grade ≥3) events occurred in 24% of patients. Although patients with preexisting autoimmune conditions displayed a statistically significant higher risk of experiencing any‑grade irAEs and discontinuation of therapy due to toxicity compared with those without autoimmune diseases, the effectiveness of treatment—measured by objective response rates, disease control rates, and survival outcomes—was comparable between the two groups. These findings underscore the need for careful patient monitoring and risk assessment but also suggest that ICIs remain a viable therapeutic option for cancer patients with concurrent autoimmune disorders.

Comparative Data Table

Below is a summary table highlighting key data metrics across the discussed studies:

Frequently Asked Questions (FAQ)

What is the significance of vascular remodeling in interstitial lung diseases?
Vascular remodeling in ILDs involves changes in the lung capillary network that directly affect disease progression. Abnormal angiogenesis, endothelial–mesenchymal transition, and changes in vessel density are linked to fibrosis. Understanding these processes may lead to targeted therapies that slow or reverse lung damage.

How does recombinant Saccharomyces cerevisiae work as a vaccine vector?
Recombinant S. cerevisiae is engineered to express target antigens (such as the FaeG protein from F4+ ETEC) on its cell surface. This design stimulates both systemic and mucosal immune responses when administered orally, leading to higher antibody production and better protection against pathogens.

Why are salusins considered potential biomarkers for IBS?
Salusins are involved in inflammatory processes and vascular regulation. Since some IBS patients exhibit low‑grade inflammation and altered gut motility, measuring salusin levels—especially salusin‑α—may provide insight into the disease state and prognosis.

What makes 3′‑deoxytubercidin a promising candidate against trypanosome infections?
3′‑Deoxytubercidin has demonstrated robust anti‑trypanosomal activity in preclinical models of Surra and Dourine with minimal toxicity. Its ability to clear parasitemia, combined with favorable pharmacokinetic properties and lower environmental toxicity, underpins its potential as a broad‑spectrum therapeutic.

Are immune checkpoint inhibitors safe for cancer patients with preexisting autoimmune diseases?
While patients with autoimmune diseases are at higher risk for immune‑related adverse events when treated with ICIs, meta‑analyses show that the overall response rates, disease control, and survival outcomes are similar to those in patients without autoimmune conditions. These results highlight the importance of close monitoring and individualized treatment plans.

References

1. Ackermann, M., Kamp, J. C., Werlein, C., et al. (2025). The role of vascularity and the fibrovascular interface in interstitial lung diseases. European Respiratory Review

2. Hu, D., Qian, P., Gao, D., et al. (2024). Recombinant Saccharomyces cerevisiae EBY100/pYD1-FaeG: A candidate for an oral subunit vaccine against F4+ ETEC infection. Applied and Environmental Microbiology. https://pubmed.ncbi.nlm.nih.gov/11784076/

3. Lowell, D., & Ford, A. (2025). Serum salusin levels in diarrhea- and constipation-predominant irritable bowel syndrome. PeerJ. https://doi.org/10.7717/peerj.18859

4. Kim, S., et al. (2025). 3′-deoxytubercidin: A potent therapeutic candidate for the treatment of Surra and Dourine. International Journal of Parasitology: Drugs and Drug Resistance. https://doi.org/10.1016/j.ijpddr.2025.100580

5. Le, J., Et al. (2025). Immune checkpoint inhibitors in cancer patients with autoimmune disease: Safety and efficacy. Human Vaccines & Immunotherapeutics